Ferritin is an iron storage protein which maintains iron in an available, non-toxic form. A variety of ferritin isoforms have been isolated from different tissues. The variability of ferritin characteristics appear to be mainly caused by the presence of different subunit types in the multimeric protein shell (Drysdale, 1977, Ciba Found. Symp. 51: 41; Arosio, et al., 1978, J. Biol. Chem. 253: 4451; Watanabe et al., 1981, Biochem. Biophys. Res. Comm. 103: 207). In fact, three ferritin subunits have been described. The L subunit (19 Kd), prevalent in iron loaded tissues, the H subunit (21 Kd), predominant in iron poor and malignant cells (Drysdale, 1977, supra; Arosio, 1978, supra) and the glycosylated G subunit (24 Kd) isolated from serum (Cragg et al., 1981, Biochem. J. 199: 565). Different isoferritins contain different proportions of L and H subunit types. More recently, preliminary analysis of cDNA clones revealed that the H and L subunits are encoded by rather complex families of genes (Brown et al., 1983, Proc. Natl. Acad. Sci. USA 73: 857; Costanzo et al., 1984, EMBO J. 3: 23), suggesting that the heterogeneity of ferritin molecules may be even greater than presently determined.
Various ferritin isoforms have been isolated from normal and malignant tissues, the most acidic ones predominating in tumor and fetal tissues (Drysdale, 1976, Ciba Found. Symp. 51: 41; Arosio et al., 1978, J. Biol. Chem. 253: 4451). It has been suggested that the assay of acidic isoferritin in the serum may be of value in the diagnosis of malignancy (Hazard et al., 1977, Nature 265: 755). Elevated concentrations of serum ferritin were found in patients suffering from a variety of malignant diseases, including acute lymphocytic leukemia (ALL) (Matzner et al., 1980, Am. J. Hematol. 9: 13), hepatoma (Giannoulis, 1984, Digestion 30: 236), breast cancer (Jacobs et al., 1976, Br. J. Cancer 34: 286), and recently Hodgkin's disease (Bezwoda et al., 1985, Scand. J. Haematol. 35: 505). In assays based on antibodies against HeLa cell ferritin, Hazard and Drysdale found higher concentrations of ferritin in sera from patients with various tumors than in the same sera assayed by antibodies directed against normal liver ferritin (Hazard, et al., supra.). Others have failed to demonstrate a consistent pattern of isoferritins in tumor tissues (Cragg et al., 1977, Br. J. Cancer 35: 635; Halliday et al., 1976, Cancer Res. 36: 4486) or in sera obtained from patients with tumors (Jones et al., 1978, Clin. Chim. Acta. 85: 81; Jones et al., 1980, Clin. Chim. Acta. 106: 203). There are, therefore, conflicting views as to the origin and specificity of the elevated serum ferritin in malignant diseases.